The Left Atrial Appendage in Humans: Structure, Physiology, and Pathogenesis

Nabeela Karim; Siew Yen Ho; Edward Nicol; Wei Li; Filip Zemrak; Vias Markides; Vivek Reddy; Tom Wong


Europace. 2020;22(1):5-18. 

In This Article

Left Atrial Appendage and its Role in Arrhythmogenesis

Embryologically, the LAA derives from the primary atrial tube, whereas the LA derives from the pulmonary vein,[1] resulting in histological differences. The discontinuity of myocardium as it transitions from LA to LAA, has been proposed as a potential substrate for arrhythmia generation.[107] Additionally, in comparison to patients in paroxysmal AF, persAF patients tend to have thicker interstitial collagen fibres which has been shown to correlate with conduction abnormalities,[108] thus, potentially contributing to arrhythmogenic substrate.

In fact, many studies implicate the LAA as a focus for electrical triggers in atrial and ventricular arrhythmias.[109–116] In atrial tachycardia involving the LAA, the mechanism has been described as predominantly that of automaticity with the majority of foci located at the LAA base[110,114] and also the distal tip.[115,116] Targeting the distal tip of the LAA has also resulted in successful termination of atrioventricular re-entrant tachycardia and ventricular tachycardia after previous failed endocardial and epicardial ablation,[112] as well as in a case of drug refractory atrial tachycardia.[114] The incidence of focal atrial tachycardia originating from the LAA been reported as between 2%[116] and 19%.[115] In AF, the prevalence of LAA firing has been reported as 27%, with 8% of cases being the sole site responsible for the AF.[113]

The impact of LAA electrical isolation on persAF ablation outcomes has shown good results, with significantly more patients remaining in sinus rhythm compared with controls.[113,117–120] In a single-centre study of 987 patients undergoing re-do persAF ablation, LAA electrical isolation vs. LAA focal ablation vs. no LAA ablation resulted in significantly less recurrence of atrial arrhythmia (AA) in the LAA electrical isolation group; 15%, 68%, and 74%, respectively.[113] In another study of 74 persAF patients undergoing stepwise AF ablation where atrial tachycardia had been mapped to the LAA (19% of cohort), ablation targeting long fractionated or mid-diastolic LAA electrograms resulted in termination of arrhythmia.[115] After 18 months without any antiarrhythmic drugs (AADs) 87% of these patients remained in sinus rhythm.[115] In a study of 846 persAF patients undergoing left atrial anterior wall ablation, LAA electrical isolation or LAA potential delay resulted in significantly less AA recurrence at 21 months; 17% compared with 46% of controls.[121] Where LAA electrical isolation occurred concomitantly with LAA occlusion in 20 persAF patients, LAA electrical isolation with stepwise AF ablation resulted in significantly higher rates of freedom of AF after 12 months, with 95% of patients remaining in sinus rhythm compared with 36% in the control group.[122] There has also been an observational study of 138 patients using suture ligation with the LARIAT device to achieve LAA electrical isolation; freedom from AF after 12 months was significantly more at 65% compared with 39% in the control group.[120] Left atrial appendage electrical isolation using cryoballoon in 100 persAF patients has also been investigated, with significant more patients (86%) remaining free of AA compared with the controls (67%) after 12 months.[123] The Belief trial is the only randomized control trial to investigate LAA electrical isolation on AF outcomes.[117] In 173 patients with long-standing persAF, 56% of the patients who underwent LAA electrical isolation remained in sinus rhythm, compared with 28% in the control group after 12 months.[117] Recently, two meta-analyses have been published on the effects of LAA electrical isolation on persAF outcomes.[118,119] In one meta-analyses, 930 patients were identified from seven studies.[119] Freedom from all AA recurrence in patients off AADs was 75.5% in the LAA electrical isolation group, which was significantly more than the 43.9% of patients who underwent standard ablation only.[119] Furthermore, no increase in acute procedural complications or risk of ischaemic stroke was identified.[119] In the other meta-analyses, 1037 persAF patients were identified from seven studies.[118] Left atrial appendage electrical isolation in addition to standard ablation was associated with significant reduction in recurrence of AF/atrial tachycardia.[118] The role of LAA in arrhythmogenesis is summarized in Supplementary material online, Table S3.

Techniques for Left Atrial Appendage Electrical Isolation

Left atrial appendage electrical isolation can be achieved with various techniques including radiofrequency ablation[112,113,115–117,121–123] cryoballoon ablation,[123] percutaneous LAA suture ligation with the Lariat device,[120] and surgical LAA occlusion using the Atriclip.[114]

Achieving LAA electrical isolation can be challenging. Acute reconnections can occur in as much as 85% of patients following radiofrequency ablation, and tend to occur anteriorly and superiorly.[122] This correlates with LAA histological analysis, which demonstrates the thickest LAA ostial areas at the anterior and superior margins.[124,125] Using the cryoballoon ablation technique for LAA electrical isolation is also associated with clinical challenges, with left circumflex artery spasm occurring in 4% of patients.[123]

Although LAA electrical isolation without LAA occlusion does not incur a significant increase in thromboembolic risk,[117–119,123] in a single-centre study of 50 patients in whom 85% were on an oral anticoagulant, LAA thrombus occurred in 20% patients, stroke in 4%, and TIA in 2%.[126] Of relevance, it has been well documented that endocardial LAA occlusion can be performed concomitantly with LAA electrical isolation during catheter ablation for AF, and is both feasible and safe.[122,127]